http://www.asmusa.org/pcsrc/40icaac/23115.htm
40th ICAAC
Interscience Conference on Antimicrobial Agents and
Chemotherapy A meeting of the American Society for Microbiology September
17-20, 2000, Toronto, Ontario, Canada For more information on any presentation
at the 40th ICAAC contact Jim Sliwa, ASM Communications at jsliwa@asmusa.org.
Evidence to suggest that we should be investigating the
inclusion of strains currently causing infection in pertussis vaccine
formulations (Session 6, Paper 61)
David Farrell
Queensland Health Pathology Service
+61 7 46316562
Results and conclusions
Sequencing of several B. pertussis genes important for
infection revealed differences in Australian strains currently causing
infection (contemporary strains) compared to strains used in vaccine
manufacture. Interestingly, these differences were identical to those described
in previous work performed by researchers in the Netherlands. In a mouse
respiratory infection model, contemporary strains were found to cause greater
lung damage than vaccine strains. Conversely, tracheal colonization and inflammation
was lower for contemporary strains. After
vaccination with current vaccine strains, challenge with a contemporary strain
resulted in a lower cell-mediated immune response (thought to be important for
long-term protection) than when the vaccine was made from the contemporary
strain. In addition, in mice vaccinated with a vaccine strain and challenged
with a contemporary strain, a markedly increased time to clear bacteria from
the lung was observed when compared to challenge with the vaccine strain (6
weeks compared to 1 week). These results suggest that an increase in time to
bacterial clearance is occurring in mice vaccinated with current vaccine
strains and challenged with contemporary strains. Contemporary strains were
found to have undetectable levels of filamentous haemagglutin, a protein that
is important for colonization of the upper respiratory tract. A limitation of
this study is the small number of strains tested. However, the data obtained
would have major implications for the selection of vaccine components.
Therefore, a larger and geographically diverse study is needed to confirm this preliminary
data.
Despite successful vaccination programs in developed
countries, infections caused by Bordetella pertussis result in significant
mortality and morbidity in humans. Hundreds of thousands of deaths, the
majority in developing countries, are attributed to pertussis annually. In
addition, adult pertussis is becoming increasingly recognized as a disease of
chronic cough in adolescents and the elderly. Although pertussis in adults is
not life threatening, it is an important cause of morbidity, economic loss due
to decreased productivity, and as a reservoir for transmission to susceptible individuals.
Immunity from vaccination is not as complete as that
obtained from natural infection and tends to wane in teenage years. Vaccine
efficacy is measured by both the immunoglobulin response and the mouse
intracerebral challenge test, neither of which assess long-term immunity. Whole
cell and acellular vaccines have been shown to be efficacious with regards to
both of these parameters. Clinical trials have failed to show a clear
correlation between serum antibody levels and protection. Cell-mediated
immunity (CMI) has been shown important in providing long-term immunity to pertussis.
There is conflicting evidence with regards to the ability of acellular
component vaccines to generate a significant CMI response, but data to date
suggests that the response is not as efficient as that generated with the whole
cell vaccines.
Changes in the genetic sequence of virulence factors used
in for vaccine production have recently been described (Mooi et al., 1998). It
is thought that these changes may be an evolutionary survival tactic by the
organism in response to vaccination. If contemporary strains of B. pertussis
differ from strains used in the production of vaccines in a significant way
(i.e. in the pathogenesis of and/or the immune response to infection) then this
phenomenon would have major implications for component selection in vaccine formulations.
The present study suggests that contemporary strains are
genetically different from vaccines (confirming the previous study in the
Netherlands) and that these differences are present in strains from
geographically diverse sites. The study also suggests that contemporary strains
produce a different disease pattern than vaccine strains and produce an altered
immune response in the host. Although pertussis vaccination has saved millions
of lives, the organism has not been eradicated. The present study may provide a
clue to the reasons why – if the organism has adapted to persist longer and cause
less damage to a previously immunized host, it is then available to be transmitted
to a non-immunized host. Inclusion of contemporary strains in current vaccines
may provide an immune response that stops carriage of the organism, diminishes
the reservoir and finally eradicates the disease.
Reference
Mooi, F.R., van Oirschot, H., Heuvelman, K., van der
Heide, H.G.J., Gaastra, W. & Willems, R.J.L. 1998, ‘Polymorphism in the
Bordetella pertussis virulence factors P.69/pertactin and pertussis toxin in
the Netherlands: temporal trends and evidence for vaccine-driven evolution’,
Infection and Immunity, vol.66, no.2, pp.670-675.
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